Cytomegalovirus encephalitis (CMV-E) of the central nervous system is common (15-20%) in patients dying of AIDS, but is rarely diagnosed in life. Neurocognitive impairment and other CNS abnormalities in AIDS patients may be caused by CMV, rather than HIV, since most HIV-infected people are concomitantly infected with CMV. If CMV infection explains some of the neurocognitive impairment, antiviral therapy for CMV may improve cognitive performance. Preliminary autopsy studies indicate that CMV-E is almost always associated with CMV retinitis (CMV-R). Thus, CMV-R may be an indicator of those at risk for CMV-E. The CMV Project will examine specific neurologic, neuropsychologic, and MRI correlates of CMV-R and CMV-E and the subsequent effects of treatment. Quantitation of CMV will be made by detection of CMV DNA after amplification by PCR in CSF, leukocytes and serum as a potential diagnostic test for CMV-E and its response to treatment. Postmortem detection of CMV and HIV in brain and eye tissue will be correlated with premortem neurocognitive, neurologic, and neuroimaging findings. The project will also explore the relationship between immunogenetic predictors (HLA alleles) and immune responses (T-cell proliferation) which we have found to predict increased risk of CMV-R. The findings of this study may a) define the role of CMV-E in cognitive impairment, neurologic symptoms, and neuroimaging abnormalities in AIDS, b) establish the reversibility of these consequences of CMV-E when treated, c) suggest two possible indicators of risk for CMV-R and CMV-E, and d) establish guidelines for virologic, ophthalmologic, and neurocognitive surveillance to provide early identification and treatment of CMV-E.